Over the past year, the Genetics Services Research Unit investigators conducted genetic counseling related research within the ClinSeq NHGRI cohort study. We present data from adults participating in ClinSeq in which perceptions of uncertainty are hypothesized to be key in predicting decisions to learn and act on genomic health information. We conducted six professionally moderated focus groups with 39 randomly selected ClinSeq participants varying on whether they had coronary heart disease and had received prior sequence results. We elicited perceptions of the uncertainties associated with genome sequencing using written prompts. Participants perceived uncertainty as a quality of genome information. The majority of participants characterized uncertainty of sequencing information as changing, fluid, developing, or ground breaking. These responses led to anticipation of more optimistic future outcomes. Fewer participants described uncertainty as questionable, less accurate, limited, or poorly understood. These perceptions seemed to undermine participants' faith in genome information, leading to feelings of disillusionment. Our findings suggest that perceptions of uncertainty are related to epistemological beliefs that inform expectations for the information. Interventions that promote realistic expectations of genome sequencing may mitigate negative responses to uncertainty. We also studied dispositional optimism and percieved risk and their affect on intentions to receive results from genome sequencing: Dispositional optimism and risk perceptions are each associated with health-related behaviors and decisions and other outcomes, but little research has examined how these constructs interact, particularly in consequential health contexts. The predictive validity of risk perceptions for health-related information seeking and intentions may be improved by examining dispositional optimism as a moderator, and by testing alternate types of risk perceptions, such as comparative and experiential risk. Participants (n = 496) had their genomes sequenced as part of a National Institutes of Health pilot cohort study (ClinSeq). Participants completed a cross-sectional baseline survey of various types of risk perceptions and intentions to learn genome sequencing results for differing disease risks (e.g., medically actionable, non-medically actionable, carrier status) and to use this information to change their lifestyle/health behaviors. Risk perceptions (absolute, comparative, and experiential) were largely unassociated with intentions to learn sequencing results. Dispositional optimism and comparative risk perceptions interacted, however, such that individuals higher in optimism reported greater intentions to learn all 3 types of sequencing results when comparative risk was perceived to be higher than when it was perceived to be lower. This interaction was inconsistent for experiential risk and absent for absolute risk. Independent of perceived risk, participants high in dispositional optimism reported greater interest in learning risks for non-medically actionable disease and carrier status, and greater intentions to use genome information to change their lifestyle/health behaviors. We also surveyed adult parents with bipolar disorder; their own adaptation to the condition and coping with risk to children. Bipolar disorder (BPD) is a common condition associated with significant morbidity and reduced quality of life. In addition to challenges caused by their mood symptoms, parents affected with BPD harbor concerns about the mental health of their children. Among adult parents who perceive themselves to have BPD, this study aims to examine participants' coping methods; identify predictors of adaptation; assess parental perceptions of risks for mood disorders among their children; and describe the relationships among illness appraisals, coping, adaptation to one's own illness, and perceived risk to one's children. Parents who self-identified as having BPD completed a web-based survey that assessed dispositional optimism, coping, perceived illness severity, perceived etiology of BPD, perceived risk to offspring, and adaptation to BPD. Participants had at least one unaffected child who was 30 years of age or below. 266 parents were included in the analysis. 87% of parents endorsed a somewhat greater or much greater risk for mood disorders in one's child(ren) than someone without a family history. Endorsing a genetic/familial etiology to BPD was positively correlated with perceived risk for mood disorders in children (rs&#8201;=&#8201;.3, p&#8201;<&#8201;0.01) and active coping with BDP (r&#8201;=&#8201;.2, p&#8201;<&#8201;0.01). Increased active coping (&#946;&#8201;=&#8201;0.4, p&#8201;<&#8201;0.001) and dispositional optimism (&#946;&#8201;=&#8201;0.3, p&#8201;<&#8201;0.001) were positively associated with better adaptation, while using denial coping was negatively associated with adaptation (&#946;&#8201;=&#8201;-0.3, p&#8201;<&#8201;0.001). The variables explained 55.2% of the variance in adaptation (F&#8201;=&#8201;73.2, p&#8201;<&#8201;0.001). Coping mediated the effect of perceived illness severity on adaptation. These data inform studies of interventions that extend beyond symptom management and aim to improve the psychological wellbeing of parents with BPD. Interventions targeted at illness perceptions and those aimed at enhancing coping should be studied for positive effects on adaptation. Parents with BPD may benefit from genetic counseling to promote active coping with their condition, and manage worry about perceived risk to their children. Children of individuals with BPD have increased risk for mood disorders and other adverse psychosocial outcomes due to genetic and environmental risk. Though parents with BPD are aware of increased risk to children, little is known about efforts undertaken in response or their perceived utility. Among parents who self-report with BPD, this study identifies key variables associated with parental coping with children's risk of mood disorders; and explores the relationship between monitoring children's moods and perceived coping efficacy. In this U.S. study, active parental coping with, and cognitive distancing from, child's risk were measured using novel scales. Parents (n = 266) who self-identified as having BPD completed a web-based survey. They had at least one unaffected child. Most participants endorsed monitoring their children's moods. Monitoring was associated with increased perceived control over the child's well-being (p < 0.005), but not feeling less worried. Active parental coping with risk to children was positively associated with active coping with own illness (&#946; = 0.25, p = 0.001), family history (&#946; = 0.24, p = 0.001), and self-report of current depression (&#946; = 0.16, p = 0.037), explaining 13.8% of the variance (F = 8.81, p < 0.001). Cognitive distancing from the child's risk was positively associated with confidence in diagnosis (&#946; = 0.25, p = 0.001), and negatively associated with self-report of current mania (&#946; = -0.19, p = 0.007), perceiving BPD as genetic (&#946; = -0.26, p < 0.001) and having more children (&#946; = -0.20, p = 0.004); explaining 16.2% of the variance (F = 8.63, p < 0.001). Parents' adaptation to their own BPD was modestly correlated with active coping with child's risk (r = 0.15, p < 0.05) but not with cognitive distancing. The findings support the importance of understanding causal attributions and the value of genetic education and counseling for parents with BPD. Further research is necessary to elucidate the psychological benefits of active coping versus cognitive distancing from child's risk, and explore additional variables that predict parental coping with children's risk of mood disorders.